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Topic:Alphavirus
Alphaviruses are a group of viruses transmitted primarily by mosquitoes and are known to cause disease in horses and humans. In equine populations, alphaviruses such as Eastern Equine Encephalitis Virus (EEEV), Western Equine Encephalitis Virus (WEEV), and Venezuelan Equine Encephalitis Virus (VEEV) are of particular concern due to their ability to cause severe neurological disease. Infection in horses can lead to symptoms ranging from fever and lethargy to more severe signs such as ataxia, paralysis, and encephalitis, often resulting in high mortality rates. Understanding the transmission dynamics, pathogenesis, and immune response in horses is crucial for developing effective prevention and control strategies. This page compiles peer-reviewed research studies and scholarly articles that explore the epidemiology, clinical presentation, diagnosis, and management of alphavirus infections in horses, as well as advancements in vaccine development and vector control methods.
Cross-Species Analysis of Transcriptomic Response to Alpha-Herpesvirus Infection in Human, Bovine and Equine Cells. Comparative transcriptomics offers a powerful approach to elucidate host-virus interactions across related pathogens, yet systematic evaluations across species-matched cellular systems remain limited. We performed a cross-species RNA sequencing analysis of respective species' cells infected with three alphaherpesviruses-herpes simplex virus 1 (HSV-1), bovine alphaherpesvirus 1 (BHV-1), and equid alphaherpesvirus 1 (EHV-1)-to dissect conserved and virus-specific transcriptional responses. We show that certain orthologous genes and orthologous pathways are differentially regulated upon infection...
Isolation of Madariaga Virus (MADV) in a Horse Coinfected with Equine Infectious Anemia in Venezuela: A Review of MADV Circulation in the Country. Madariaga virus (MADV), formerly known as the South American variant of Eastern Equine Encephalitis virus (EEEV), is an alphavirus that belongs to the family and has been periodically infecting equids in Venezuela since its first identification in 1975. This study reports the isolation and molecular characterization of MADV isolated from a horse in December 2024 in the context of MADV cases reported in Venezuela. Methods: Antibodies to the rabies virus were detected by indirect immunofluorescence, and to the Equine Infectious Anemia virus (EIAV) by passive immunodiffusion. MADV RNA was detect...
Structural insights into VLDLR recognition by western equine encephalitis virus. Western equine encephalitis virus (WEEV), a group of encephalitic alphaviruses that cause severe diseases in humans and equids, historically used the very-low-density lipoprotein receptor (VLDLR) as a receptor during infection. However, current epidemic strains no longer use VLDLR as a receptor. In this study, we identify that LA1, LA2, LA3, and LA5 of VLDLR can directly interact with WEEV. Using cryo-electron microscopy, we investigate the structures of complexes formed between WEEV and VLDLR-LBD or other VLDLR fragments. Our findings show that LA1 and LA2 insert into a cleft formed by two ad...
Western equine encephalitis virus: A comprehensive review of epidemics, transmission, hosts, and strategies for mitigation. Recent increases in cases of western equine encephalitis (WEE) in South America have raised significant concerns about the virus's potential to cause an endemic disease due to its adaptation to mosquito vectors. Currently, there are no effective vaccines or treatments for WEEV, despite ongoing research into various biochemical products in animal models. The virus presents different pathological effects depending on the host. In humans, WEEV infection leads to central nervous system damage, resulting in encephalitis and severe neurological sequelae, which underscores the need for further resear...
A retrospective study of 171 cases of equine meningoencephalomyelitis in the United States, 1996-2023. Equine meningoencephalomyelitis is an important cause of morbidity and mortality and is associated with a wide variety of infectious etiologies. Because of the lack of large retrospective studies, the prevalence and incidence of these diseases are unknown. Here we describe 171 cases of meningoencephalomyelitis in horses submitted to the Section of Anatomic Pathology at the New York State Animal Health Diagnostic Center (Cornell University, Ithaca, NY, USA) from 1996-2023. Neuroinflammatory disease was identified in 5.4% of submitted horses with a wide breed, age, and sex distribution. A parasi...
V4020 Venezuelan Equine Encephalitis Vaccine: Mitigating Neuroinvasion and Reversion Through Rational Design. There is a need for safe and effective vaccines against the Venezuelan equine encephalitis virus that infects both humans and equines. However, development of a live-attenuated vaccine using the TC-83 strain has been hampered by substantial reactogenicity and the potential for neuroinvasion. In this study, we demonstrate that V4020, a new TC-83-based investigational VEEV vaccine with redundant safety features preventing neuroinvasion and reversion, exhibited no neuroinvasion potential in a murine model. Following subcutaneous or intramuscular administration, a subset of mice that received the ...
From transmission to adaptive evolution: genomic surveillance of Getah virus. Getah virus (GETV) is a member of the of the . It is a single-stranded positive-RNA virus that is mainly transmitted by mosquitoes. In recent years, the spread of GETV has become increasingly serious, causing serious losses to the animal economy and posing a potential threat to public health. GETV infected animals extend from traditional domestic animals such as horses and pigs to cattle, foxes and other animals. Especially in China, the virus has been detected in many provinces in recent years. In addition, GETV-specific antibodies were detected in healthy humans. However, the threat posed b...
Equine viral arteritis: Seroprevalence patterns and risk factors in equids from western Europe. Equine viral arteritis is a notifiable infectious disease with sanitary and economic implications at a global scale. A cross-sectional serosurvey was performed to determine the exposure of equids to the Alphaarterivirus equid [Equine Arteritis Virus (EAV)] in three regions in western Europe. Serum samples from 1425 equids (1196 horses, 104 donkeys, and 125 mules/hinnies) from Catalonia (northeastern Spain), Andalusia (southern Spain) and southeastern United Kingdom (UK) were collected during the period 2011-2023. The overall EAV seroprevalence in EAV-unvaccinated equids was 9.7 % (138/1425; 9...
Local Circulation of Sindbis Virus in Wild Birds and Horses, the Netherlands, 2021-2022. We report Sindbis virus circulation in the Netherlands based on serologic evidence found in 6 resident wild birds and 3 horses (2021-2022). Tested mosquitoes were molecularly negative, and humans were serologically negative. Veterinarians and health practitioners in the Netherlands should be aware of the importance of surveillance for Sindbis virus.
Distinct cellular and molecular responses to infection in three target cell types from horses, a species naturally susceptible to Ross River virus. Our current understanding of the pathogenesis of Ross River virus (RRV) infection has been derived from murine models, which do not reproduce clinical disease as experienced by infected humans and horses. This prompted us to establish more relevant host model systems to study host-virus interactions using ex vivo peripheral blood mononuclear cells (PBMCs) and in vitro primary synovial fibroblast and epidermal keratinocyte cultures. Transcriptomic analysis revealed that the expression of the transmembrane protein matrix remodelling associated 8 (mxra8), recently found to be responsible for RRV ...
Molecular basis for shifted receptor recognition by an encephalitic arbovirus. After decades of inactivity throughout the Americas, western equine encephalitis virus (WEEV) recently re-emerged in South America, causing a large-scale outbreak in humans and horses. WEEV binds protocadherin 10 (PCDH10) as a receptor; however, nonpathogenic strains no longer bind human or equine PCDH10 but retain the ability to bind avian receptors. Highly virulent WEEV strains can also bind the very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) as alternative receptors. Here, by determining cryo-electron microscopy structures of WEEV strains isolated from...
Diagnosis and genomic characterization of the largest western equine encephalitis virus outbreak in Uruguay during 2023-2024. The Western equine encephalitis virus is transmitted between mosquitoes and wild birds. Mosquitoes spread the virus to horses and human populations, causing severe encephalitis and death. The most recent large outbreak occurred in South America from November 2023 to April 2024. We identified and genetically characterized Uruguayan strains during this outbreak to understand their evolutionary trends and rapid expansion. We obtained genomes from 15 strains using a novel multiplex PCR assay combined with next-generation Illumina sequencing. The phylogenetic analysis revealed that viruses from Uru...
Eastern Equine Encephalitis Virus: The Importance of Metabolism and Aging. Eastern equine encephalitis virus (EEEV) is a mosquito-transmitted alphavirus that, among humans, can cause a severe and often fatal illness. The zoonotic EEEV enzootic cycle involves a cycle of transmission between and avian hosts, frequently resulting in spillover to dead-end vertebrate hosts such as humans and horses. Interestingly, it has been described that the W132G mutation of the very low-density lipoprotein receptor (VLDLR), the receptor of EEEV, significantly enhanced the VLDLR-mediated cell attachment of EEEV. The patient's metabolism plays a pivotal role in shaping the complex lan...
Genetic, Phylogenetic, and Serological Analysis of a Getah Virus Strain Isolated from Culex tritaeniorhynchus Mosquitoes in Nagasaki, Japan in 2022. Getah virus (GETV), belonging to the genus Alphavirus within the family Togaviridae, is a mosquito-borne virus that causes fever, rash, edema in horses, fatalities, and pregnancy disorders in pigs. It has caused occasional outbreaks in horse populations in Japan, China, and India, and the endemic areas are gradually expanding, particularly in Asia and Oceania. In this study, we isolated a new GETV strain from Culex tritaeniorhynchus mosquitoes collected in Nagasaki Prefecture, Japan, in 2022. Phylogenetic analysis demonstrated that this new strain, 22IH8, was more closely related to previous C...
Attenuated Getah virus confers protection against multiple arthritogenic alphaviruses. Alphaviruses are important arthropod-transmitted pathogens of humans and livestock. Getah virus (GETV) is an arthritogenic alphavirus that causes disease in horses and piglets; it also poses a potential threat to humans. A live attenuated vaccine candidate named GETV-3ΔS2-CM1, harbouring a deletion in nonstructural protein 3 and substitutions in the capsid protein, is genetically stable and exhibits robust immunogenicity. It was shown to confer passive protection to piglets born to immunized sows. In mice, a single dose of GETV-3ΔS2-CM1 protected against infection with different strains of G...
Equine Encephalomyelitis Outbreak, Uruguay, 2023-2024. We report the genomic analysis from early equine cases of the Western equine encephalitis virus outbreak during 2023-2024 in Uruguay. Sequences are related to a viral isolate from an outbreak in 1958 in Argentina. A viral origin from South America or continuous enzootic circulation with infrequent spillover is possible.
Outbreak of Western Equine Encephalitis Virus Infection Associated with Neurological Disease in Horses Following a Nearly 40-Year Intermission Period in Argentina. Western equine encephalitis virus (WEEV) is a mosquito-borne arbovirus (genus , family ) that has re-emerged in South America in late 2023, causing severe disease in both horses and humans after a nearly 40-year intermission period. We here describe the virological, serological, pathological, and molecular features of WEEV infection in horses during the 2023-2024 outbreak in Argentina. WEEV-infected horses developed neurological signs with mild to severe encephalitis associated with minimal to abundant WEEV-infected cells, as demonstrated by WEEV-specific in situ hybridization. The distributio...
Molecular Epidemiology of Western Equine Encephalitis Virus, South America, 2023-2024. Western equine encephalitis virus (WEEV) is a mosquitoborne virus that reemerged in December 2023 in Argentina and Uruguay, causing a major outbreak. We investigated the outbreak using epidemiologic, entomological, and genomic analyses, focusing on WEEV circulation near the Argentina‒Uruguay border in Rio Grande do Sul state, Brazil. During November 2023‒April 2024, the outbreak in Argentina and Uruguay resulted in 217 human cases, 12 of which were fatal, and 2,548 equine cases. We determined cases on the basis of laboratory and clinical epidemiologic criteria. We characterized 3 fatal equ...
Shifts in receptors during submergence of an encephalitic arbovirus. Western equine encephalitis virus (WEEV) is an arthropod-borne virus (arbovirus) that frequently caused major outbreaks of encephalitis in humans and horses in the early twentieth century, but the frequency of outbreaks has since decreased markedly, and strains of this alphavirus isolated in the past two decades are less virulent in mammals than strains isolated in the 1930s and 1940s. The basis for this phenotypic change in WEEV strains and coincident decrease in epizootic activity (known as viral submergence) is unclear, as is the possibility of re-emergence of highly virulent strains. Here...
A recombinant Getah Virus expressing a GFP gene for rapid neutralization testing and antiviral drug screening assay. Getah virus (GETV) is a re-emerging mosquito-borne RNA virus that induces fever, hind limb edema, swollen submandibular lymph nodes, and urticaria in horses. In pigs, the virus often results in stillbirths among pregnant sows, and neurological symptoms leading to death in piglets. Currently, there are no specific treatments or drugs available for GETV infection. The use of reporter viruses to monitor viral replication and spread in real-time within infected cells and animals provides a powerful tool for targeting antiviral drugs throughout the viral life cycle. Their fluorescence-tracked chara...
Development and application of a colloidal-gold immunochromatographic strip for detecting Getah virus antibodies. Getah virus (GETV) is a re-emerging mosquito-borne alphavirus that is highly pathogenic, mainly to pigs and horses. There are no vaccines or treatments available for GETV in swine in China. Therefore, the development of a simple, rapid, specific, and sensitive serological assay for GETV antibodies is essential for the prevention and control of GETV. Current antibody monitoring methods are time-consuming, expensive, and dependent on specialized instrumentation, and these features are not conducive to rapid detection in clinical samples. To address these problem, we developed immunochromatograph...
Exposure dynamics of Ross River virus in horses – Horses as potential sentinels (a One Health approach). Ross River virus (RRV), the most medically and economically important arbovirus in Australia, has been the most prevalent arbovirus infections in humans for many years. Infected humans and horses often suffer similar clinical symptoms. We conducted a prospective longitudinal study over a 3.5-year period to investigate the exposure dynamics of RRV in three foal cohorts (n = 32) born in a subtropical region of South East Queensland, Australia, between 2020 and 2022. RRV-specific seroconversion was detected in 56% (n = 18) of foals with a median time to seroconversion, after waning of materna...
Venezuelan Equine Encephalitis Venezuelan Equine Encephalitis Virus (VEEV) is the causative viral pathogen of Venezuelan Equine Encephalitis (VEE). Outbreaks frequently involve both equines – including horses, donkeys, mules, zebras – and humans. Outbreaks may range over a large geographic area and may last for several months to years. Sporadic epidemic outbreaks occur most commonly in Central and South America. VEEV exists as both a natural pathogen and a laboratory-developed biologic weapon. Outbreaks have been reported in several South and Central American countries, including Venezuela, Colombia, Peru, Ecuador, C...
Eastern Equine Encephalitis Virus Diversity in Massachusetts Patients, 1938-2020. Eastern equine encephalitis virus (EEEV) is a relatively little-studied alphavirus that can cause devastating viral encephalitis, potentially leading to severe neurological sequelae or death. Although case numbers have historically been low, outbreaks have been increasing in frequency and scale since the 2000 s. It is critical to investigate EEEV evolutionary patterns, especially within human hosts, to understand patterns of emergence, host adaptation, and within-host evolution. To this end, we obtained formalin-fixed paraffin-embedded tissue blocks from discrete brain regions from five contem...
Efficacy of a brain-penetrant antiviral in lethal Venezuelan and eastern equine encephalitis mouse models. Venezuelan and eastern equine encephalitis viruses (VEEV and EEEV, respectively) are mosquito-borne, neuroinvasive human pathogens for which no FDA-approved therapeutic exists. Besides the biothreat posed by these viruses when aerosolized, arthropod transmission presents serious health risks to humans, as demonstrated by the 2019 outbreak of EEE disease in the United States that resulted in 38 confirmed cases, 19 deaths, and neurological effects in survivors. Here, we describe the discovery of a 2-pyrrolidinoquinazolinone scaffold, efficiently synthesized in two to five steps, whose structural...
Mapping Eastern (EEE) and Venezuelan Equine Encephalitides (VEE) among Equines Using Geographical Information Systems, Colombia, 2008-2019. Eastern equine encephalitis virus (EEEV) and Venezuelan equine encephalitis virus (VEEV) viruses are zoonotic pathogens affecting humans, particularly equines. These neuroarboviruses compromise the central nervous system and can be fatal in different hosts. Both have significantly influenced Colombia; however, few studies analyse its behaviour, and none develop maps using geographic information systems to characterise it. To describe the temporal-spatial distribution of those viruses in Colombia between 2008 and 2019. Retrospective cross-sectional descriptive study, based on weekly reports by ...
Codon usage bias of Venezuelan equine encephalitis virus and its host adaption. Venezuelan equine encephalitis virus (VEEV) is an emerging zoonotic virus in the alphavirus genus. It can be transmitted to humans due to spillover from equid-mosquito cycles. The symptoms caused by VEEV include fever, headache, myalgia, nausea, and vomiting. It can also cause encephalitis in severe cases. The evolutionary features of VEEV are largely unknown. In this study, we comprehensively analyzed the codon usage pattern of VEEV by computing a variety of indicators, such as effective number of codons (ENc), codon adaptation index (CAI), relative synonymous codon usage (RSCU), on 130 VEEV ...
Eastern, Western, and Venezuelan Equine Encephalitis and West Nile Viruses: Clinical and Public Health Considerations. The continued recognition and emergence of alphavirus and flavivirus diseases is a growing veterinary and public health concern. As the global environment continues to change, mosquito-borne diseases will continue to evolve and expand. Continued development of readily available vaccines for the prevention of these diseases in humans and animals is essential to controlling epizootics of these diseases. Further research into effective antiviral treatments is also sorely needed. This article describes equine encephalitis viruses with a focus on clinical and public health considerations.
Advances in the Development of Small Molecule Antivirals against Equine Encephalitic Viruses. Venezuelan, western, and eastern equine encephalitic alphaviruses (VEEV, WEEV, and EEEV, respectively) are arboviruses that are highly pathogenic to equines and cause significant harm to infected humans. Currently, human alphavirus infection and the resulting diseases caused by them are unmitigated due to the absence of approved vaccines or therapeutics for general use. These circumstances, combined with the unpredictability of outbreaks-as exemplified by a 2019 EEE surge in the United States that claimed 19 patient lives-emphasize the risks posed by these viruses, especially for aerosolized V...
Epidemiological and Genomic Characterisation of Middelburg and Sindbis Alphaviruses Identified in Horses with Febrile and Neurological Infections, South Africa (2014-2018). Although Old World alphaviruses, Middelburg- (MIDV) and Sindbis virus (SINV), have previously been detected in horses and wildlife with neurologic disease in South Africa, the pathogenesis and clinical presentation of MIDV and SINV infections in animals are not well documented. Clinical samples from horses across South Africa with acute or fatal neurologic and febrile infections submitted between 2014-2018 were investigated. In total, 69/1084 (6.36%) and 11/1084 (1.01%) horses tested positive for MIDV and SINV, respectively, by real-time reverse transcription (RT) PCR. Main signs/outcomes for ...
